The present invention relates to surface modifications of pyrolytic carbon and to a method for effecting such modifications.
Pyrolytic carbon is one material of choice for use in vivo devices where relatively long term exposure to blood can be expected, such as prosthetic heart valves, the morphology of which has been reported by Goodman et al., xe2x80x9cThree-dimensional Morphology and Platelet Adhesion on Pyrolytic Carbon Heart Valve Materials,xe2x80x9d Cells and Materials, Vol. 5, No. 1, pp. 15-30 (Scanning Electron Microscopy International, 1995). Pyrolytic carbon is not only effective in increasing the strength of the in vivo device but it also exhibits improved wear-resistant characteristics and deterioration even when implanted within the body for long periods of time.
In some biomedical applications, a more wear-resistance surface is required. One way of modifying pyrolytic carbon for such uses includes alloying the pyrolytic carbon with a silicon carbide base, which is described by King et al., xe2x80x9cSurface Analysis of Silicon: Alloyed and Unalloyed LTI Pyrolytic Carbon,xe2x80x9d Photon, Electron, and Ion Probes, ACS Symposium Series 162, Washington, D.C. (1981). Additionally, it may be desirable to modify a carbon surface to enhance biocompatibility. LaGrange et al. described methods for attaching heparin with and without benzalkonium chloride on a porous carbon surface. LaGrange et al., xe2x80x9cCompatibility of Carbon and Blood,xe2x80x9d National Heart Institute, Artificial Heart Program, Artificial Heart Program Conference Proceedings, Chapter 5, (1969). McPherson et al. describes an alternate method for reducing thrombogenicity of an inorganic surface, such as glass, nitinol, and pyrolytic carbon primed with trichlorovinylsilane by grafting poly(ethylene oxide) or a poly(ethylene oxide) surfactant on the inorganic surface using gamma radiation. McPherson et al., xe2x80x9cCovalent Grafting of PEO to Inorganic Surfaces,xe2x80x9d J. Biomedical Materials, Vol. 38:289-302 (1997).
What is yet needed is a method for surface modifying a pyrolytic carbon surface, for example in an in vivo device, in such a way so as to be useful in promoting adhesion when attaching a polymer to the surface of an implantable device.
One aspect of the present invention provides a method for modifying a pyrolytic carbon surface including providing a substrate having at least one pyrolytic carbon surface to a reaction chamber; depositing an oxygen-containing, silicon-containing film forming monomer on the at least one pyrolytic carbon surface; and priming the at least one pyrolytic carbon surface having the oxygen-containing, silicon-containing film forming monomer deposited thereon with a organosilane compound.
As used herein, xe2x80x9csilanexe2x80x9d and xe2x80x9corganosilanexe2x80x9d refer to a saturated linear branched or unbranched compound having the nonhydrolyzed formula RnSiM4xe2x88x92n, wherein n is preferably greater than 1. Preferably, M is selected from the group consisting of a halogen, a alkoxy group, an acyloxy group, or an amine group. R is preferably a hydrocarbon group that is classified as an aliphatic group, cyclic group, or a combination of aliphatic and cyclic groups (e.g., alkaryl and aralkyl groups). In the context of the present invention, the term xe2x80x9caliphatic groupxe2x80x9d means a saturated or unsaturated linear or branched hydrocarbon group. This term is used to encompass alkyl, alkenyl, and alkynyl groups, for example. The term xe2x80x9calkyl groupxe2x80x9d means a saturated linear or branched hydrocarbon group, including, for example, methyl, ethyl, isopropyl, t-butyl, heptyl, dodecyl, octadecyl, amyl, 2-ethylhexyl, and the like. The term xe2x80x9calkenyl groupxe2x80x9d means an unsaturated linear or branched hydrocarbon group with one or more carbon-carbon double bonds, such as a vinyl group. The term xe2x80x9calkynyl groupxe2x80x9d means an unsaturated linear or branched hydrocarbon group with one or more triple bonds. The term xe2x80x9ccyclic groupxe2x80x9d means a closed ring hydrocarbon group that is classified as an alicyclic group, aromatic group, or heterocyclic group. The term xe2x80x9calicyclic groupxe2x80x9d means a cyclic hydrocarbon group having properties resembling those of aliphatic groups. The term xe2x80x9caromatic groupxe2x80x9d or xe2x80x9caryl groupxe2x80x9d means a mono- or polynuclear aromatic hydrocarbon group. The term xe2x80x9cheterocyclic groupxe2x80x9d means a closed ring hydrocarbon in which one or more of the atoms in the ring is an element other than carbon (e.g., nitrogen, oxygen, sulfur, etc.).
The term xe2x80x9cgroupxe2x80x9d is used to describe a chemical substituent that includes the unsubstituted group and the group with nonperoxidic O, N, or S atoms, for example, in the chain as well as carbonyl groups or other conventional substitution. For example, the phrase xe2x80x9calkyl groupxe2x80x9d is intended to include not only pure open chain saturated hydrocarbon alkyl substituents, such as methyl, ethyl, propyl, t-butyl, and the like, but also alkyl substituents bearing further substituents known in the art, such as hydroxy, alkoxy, alkylsulfonyl, halogen atoms, cyano, nitro, amino, carboxyl, etc. Thus, xe2x80x9calkyl groupxe2x80x9d includes ether groups, haloalkyls, nitroalkyls, carboxylalkyls, hydroxylalkyls, sulfoalkyls, etc. Preferably, the oxygen-containing, silicon-containing film forming monomer comprises a siloxane, preferably an organosiloxane.
As used herein, xe2x80x9csiloxanexe2x80x9d and xe2x80x9corganosiloxanexe2x80x9d refer to a linear or cyclic oxygen-containing, silicon-containing compound having the general formula (Sixe2x80x94Oxe2x80x94Si)zRxe2x80x23x, wherein Rxe2x80x2 is a hydrocarbon group that is preferably an aliphatic group, further wherein z is 1 or more and x is 1 or more. When x is more than 1, Rxe2x80x2 can each be the same or a different hydrocarbon group. In the context of the present invention, the term xe2x80x9caliphatic groupxe2x80x9d means a saturated or unsaturated linear or branched hydrocarbon group. This term is used to encompass alkyl, alkenyl, and alkynyl groups, for example. The term xe2x80x9calkyl groupxe2x80x9d means a saturated linear or branched hydrocarbon group, including, for example, methyl, ethyl, isopropyl, t-butyl, heptyl, dodecyl, octadecyl, amyl, 2-ethylhexyl, and the like. The term xe2x80x9calkenyl groupxe2x80x9d means an unsaturated linear or branched hydrocarbon group with one or more carbon-carbon double bonds, such as a vinyl group. The term xe2x80x9calkynyl groupxe2x80x9d means an unsaturated linear or branched hydrocarbon group with one or more triple bonds. Preferably, Rxe2x80x2 has the general formula (CyH2y+1).
A method in accordance with the present invention may further include the step of adding a polymer to the at least one pyrolytic carbon surface primed with the silane compound. Preferably, the polymer is selected from the group consisting of a natural hydrogel, a synthetic hydrogel, teflon, silicone, polyurethane, polysulfone, cellulose, polyethylene, polypropylene, polyamide, polyimide, polyester, polytetrafluoroethylene, polyvinyl chloride, epoxy, phenolic, neoprene, polyisoprene, and a combination thereof.
A method in accordance with the present invention may also include a step of adding a bio-active compound to the at least one pyrolytic carbon surface primed with the silane compound. Preferably, the bio-active compound is selected from the group consisting of an antithrombotic agent, an antiplatelet agent, an antimitotic agent, an antioxidant, an antimetabolite agent, an anti-inflammatory agent, and a combination thereof.
The step of depositing an oxygen-containing, silicon-containing film forming monomer on the at least one pyrolytic carbon surface preferably includes plasma depositing the film forming monomer in the presence of an inert gas. Typically, the inert gas is selected from the group of argon, helium, nitrogen, neon, and a combination thereof. If an inert gas is included, the film forming monomer is preferably in a ratio with the inert gas of about 20 parts film forming monomer to about 1 part inert gas.
In a method in accordance with the present invention, plasma depositing the film forming monomer occurs for a time period from about 10 minutes or less, preferably about 15 seconds to about 4 minutes.
Another aspect of the present invention provides a method of increasing adhesion between a pyrolytic carbon surface and a polymer. The method includes the steps of providing a substrate having at least one pyrolytic carbon surface to a reaction chamber; depositing an oxygen-containing, silicon-containing film forming monomer on the at least one pyrolytic carbon surface; priming the at least one pyrolytic carbon surface having the oxygen-containing, silicon-containing film forming monomer deposited thereon with a silane compound; and adding a polymer to the at least one pyrolytic carbon surface primed with the silane compound.
A further aspect of the present invention provides a method for attaching a polymer to a prosthetic heart valve comprising at least one pyrolytic carbon surface. The method includes the steps of forming a film on the at least one pyrolytic carbon surface of the heart valve, wherein the film is formed from an oxygen-containing, silicon-containing film forming monomer; priming the at least one pyrolytic carbon surface having the oxygen-containing, silicon-containing film forming monomer film thereon with a silane compound; and adding silicone to the at least one pyrolytic carbon surface primed with the silane compound.
Also provided is a modified pyrolytic carbon surface exhibiting increased adhesion to a polymer produced by a method in accordance with the present invention, wherein a wet adhesion peel force of the modified pyrolytic carbon surface and the polymer is at least 10 times greater than the wet adhesion peel force between an unmodified pyrolytic carbon and silicone rubber as measured by ASTM D 903-49 after 28 days in an aqueous environment.